Although methamphetamine has long been endemic to the Portland, Oregon region, its use has reached[unreadable] epidemic proportions nationally. Several studies have reported poor retention of stimulant abusors entering[unreadable] treatment, consistent with the 50% rate of our outpatient clinic. Unfortunately, there is no clinically approved[unreadable] medication to alleviate the severe aversive symptoms that accompany early abstinence from[unreadable] methamphetamine. Recent studies in cocaine abusers entering community day hospital treatment have[unreadable] shown that the beta antagonist propranolol decreases these aversive symptoms while increasing retention[unreadable] and abstinence rates. Hospitalized methamphetamine abusers entering outpatient treatment upon[unreadable] discharge, have comparable or greater amounts of aversive symptomatology. Preclinical stress induced[unreadable] reinstatement studies (in animals whose prior self administration is extinguished pior to stress) hypothesize[unreadable] that beta blockers protect against stress induced relapse. The purpose of the current grant is translational[unreadable] research testing this preclinical hypothesis as well as extending its application from cocaine to[unreadable] methamphetamine in two eighty patient double blind inpatient initiated eight week outpatient trials. Since[unreadable] the preclinical studies model relapse in abstinent patients all patients will be enrolled immediately after a[unreadable] recent hospitalization. Clinical Trial I will evaluate carvedilol, a beta antagonist with additional[unreadable] neuroprotective properties and alpha antagonist properties (believed to be safer in those patients who[unreadable] relapse to methamphetamine while on study medication). In Clinical Trial II, the goal will be translational[unreadable] research based on findings from Years 1-2 utilizing a cholinergic medication identified by Scientific[unreadable] Component 1. In addition, patients will undergo, after four weeks of study medication, a human laboratory[unreadable] evaluation of stressor responsivity. It has been hypothesized that increased stress responsivity is a long term[unreadable] neuroadaptation to drug abuse that may permanently increase the risk of stress-induced relapse.